Tumor Suppressor Candidate 2 (TUSC2): Discovery, Functions, and Cancer Therapy.
N-terminal myristoylation
TUSC2
apoptosis
cancer
mitochondrial calcium homeostasis
tumor suppressor
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
25 Apr 2023
25 Apr 2023
Historique:
received:
24
03
2023
revised:
20
04
2023
accepted:
23
04
2023
medline:
13
5
2023
pubmed:
13
5
2023
entrez:
13
5
2023
Statut:
epublish
Résumé
Tumor Suppressor Candidate 2 (TUSC2) was first discovered as a potential tumor suppressor gene residing in the frequently deleted 3p21.3 chromosomal region. Since its discovery, TUSC2 has been found to play vital roles in normal immune function, and TUSC2 loss is associated with the development of autoimmune diseases as well as impaired responses within the innate immune system. TUSC2 also plays a vital role in regulating normal cellular mitochondrial calcium movement and homeostasis. Moreover, TUSC2 serves as an important factor in premature aging. In addition to TUSC2's normal cellular functions, TUSC2 has been studied as a tumor suppressor gene that is frequently deleted or lost in a multitude of cancers, including glioma, sarcoma, and cancers of the lung, breast, ovaries, and thyroid. TUSC2 is frequently lost in cancer due to somatic deletion within the 3p21.3 region, transcriptional inactivation via TUSC2 promoter methylation, post-transcriptional regulation via microRNAs, and post-translational regulation via polyubiquitination and proteasomal degradation. Additionally, restoration of TUSC2 expression promotes tumor suppression, eventuating in decreased cell proliferation, stemness, and tumor growth, as well as increased apoptosis. Consequently, TUSC2 gene therapy has been tested in patients with non-small cell lung cancer. This review will focus on the current understanding of TUSC2 functions in both normal and cancerous tissues, mechanisms of TUSC2 loss, TUSC2 cancer therapeutics, open questions, and future directions.
Identifiants
pubmed: 37173921
pii: cancers15092455
doi: 10.3390/cancers15092455
pmc: PMC10177220
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : R01CA228137-01A1
Pays : United States
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